Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: Insights into mechanisms of familial Parkinson's disease

Judy C. Triplett, Zhaoshu Zhang, Rukhsana Sultana, Jian Cai, Jon B. Klein, Hansruedi Büeler, David Allan Butterfield

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Parkinson's disease (PD) is an age-related, neurodegenerative motor disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and presence of α-synuclein-containing protein aggregates. Mutations in the mitochondrial Ser/Thr kinase PTEN-induced kinase 1 (PINK1) are associated with an autosomal recessive familial form of early-onset PD. Recent studies have suggested that PINK1 plays important neuroprotective roles against mitochondrial dysfunction by phosphorylating and recruiting Parkin, a cytosolic E3 ubiquitin ligase, to facilitate elimination of damaged mitochondria via autophagy-lysosomal pathways. Loss of PINK1 in cells and animals leads to various mitochondrial impairments and oxidative stress, culminating in dopaminergic neuronal death in humans. Using a 2-D polyacrylamide gel electrophoresis proteomics approach, the differences in expressed brain proteome and phosphoproteome between 6-month-old PINK1-deficient mice and wild-type mice were identified. The observed changes in the brain proteome and phosphoproteome of mice lacking PINK1 suggest that defects in signaling networks, energy metabolism, cellular proteostasis, and neuronal structure and plasticity are involved in the pathogenesis of familial PD.

Original languageEnglish
Pages (from-to)750-765
Number of pages16
JournalJournal of Neurochemistry
Volume133
Issue number5
DOIs
StatePublished - Jun 1 2015

Bibliographical note

Publisher Copyright:
© 2015 International Society for Neurochemistry.

Keywords

  • Expression proteomics
  • Knockout mouse
  • PINK1
  • Parkinson's disease
  • phosphoproteomics

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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